Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

An exploratory mixed methods study of the acceptability and effectiveness of mindfulness -based cognitive therapy for patients with active depression and anxiety in primary care

BACKGROUND: Mindfulness Based Cognitive Therapy (MBCT) is an 8-week course developed for patients with relapsing depression that integrates mindfulness meditation practices and cognitive theory. Previous studies have demonstrated that non-depressed participants with a history of relapsing depression are protected from relapse by participating in the course. This exploratory study examined the acceptability and effectiveness of MBCT for patients in primary care with active symptoms of depression and anxiety METHODS: 13 patients with recurrent depression or recurrent depression and anxiety were recruited to take part in the study. Semi-structured qualitative interviews were conducted three months after completing the MBCT programme. A framework approach was used to analyse the data. Beck depression inventories (BDI-II) and Beck anxiety inventories (BAI) provided quantitative data and were administered before and three months after the intervention. RESULTS: The qualitative data indicated that mindfulness training was both acceptable and beneficial to the majority of patients. For many of the participants, being in a group was an important normalising and validating experience. However most of the group believed the course was too short and thought that some form of follow up was essential. More than half the patients continued to apply mindfulness techniques three months after the course had ended. A minority of patients continued to experience significant levels of psychological distress, particularly anxiety. Statistically significant reductions in mean depression and anxiety scores were observed; the mean pre-course depression score was 35.7 and post-course score was 17.8 (p = 0.001). A similar reduction was noted for anxiety with a mean pre-course anxiety score of 32.0 and mean post course score of 20.5 (p = 0.039). Overall 8/11 (72%) patients showed improvements in BDI and 7/11 (63%) patients showed improvements in BAI. In general the results of the qualitative analysis agreed well with the quantitative changes in depression and anxiety reported. CONCLUSION: The results of this exploratory mixed methods study suggest that mindfulness based cognitive therapy may have a role to play in treating active depression and anxiety in primary care

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

<p>Abstract</p> <p>Background</p> <p>In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.</p> <p>Methods</p> <p>Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.</p> <p>Results</p> <p>At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia.</p> <p>Conclusion</p> <p>In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control.</p

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum α-fetoprotein (AFP) and human chorionic gonadotrophin-β (hCGβ) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGβ. α-Fetoprotein and hCGβ were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. α-Fetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGβ levels, and worse survival. Human chorionic gonadotrophin-β levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. α-Fetoprotein and hCGβ are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGβ are clinically important in NETs and when elevated are poor prognostic markers

Anatomic and histological study of the anterolateral aspect of the knee: a SANTI Group investigation

Background: The structure and function of the anterolateral aspect of the knee have been significantly debated, with renewed interest in this topic since the description of the anterolateral ligament (ALL). Purpose: To define and describe the distinct structures of the lateral knee and to correlate the macroscopic and histologic anatomic features. Study Design: Descriptive laboratory study. Methods: Twelve fresh-frozen human cadavers were used for anatomic analysis. In the left knee, a layer-by-layer dissection and macroscopic analysis were performed. In the right knee, an en bloc specimen was obtained encompassing an area from the Gerdy tubercle to the posterior fibular head and extending proximally from the anterior aspect to the posterior aspect of the lateral femoral epicondyle. The en bloc resection was then frozen, sliced at the level of the joint line, and reviewed by a musculoskeletal pathologist. Results: Macroscopically, the lateral knee has 4 main layers overlying the capsule of the knee: the aponeurotic layer, the superficial layer including the iliotibial band (ITB), the deep fascial layer, and the ALL. Histologically, 8 of 12 specimens demonstrated 4 consistent, distinct structures: the ITB, the ALL, the lateral collateral ligament, and the meniscus. Conclusion: The lateral knee has a complex orientation of layers and fibers. The ALL is a distinct structure from the ITB and is synonymous to the previously described capsulo-osseous layer of the ITB. Clinical Relevance: Increasingly, lateral extra-articular procedures are performed at the time of anterior cruciate ligament reconstruction. Understanding the anatomic features of the anterolateral aspect of the knee is necessary to understand the biomechanics and function of the structures present and allows surgeons to attempt to replicate those anatomic characteristics when performing extra-articular reconstruction

WriteSim TCExam - An open source text simulation environment for training novice researchers in scientific writing

BACKGROUND: The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers) RESULTS: The development process was guided by feedback from usability tests within our research team. Online surveys and formal studies, involving members of the Research on Research group and selected novice researchers, show that the application is user-friendly. Additionally it has been used to train 25 novice researchers in scientific writing to date and has generated encouraging results. CONCLUSION: WriteSim TCExam is the first Web-based, open-source textual simulation environment designed to complement traditional scientific writing instruction. While initial reviews by students and educators have been positive, a formal study is needed to measure its benefits in comparison to standard instructional methods

Robotic-assisted laparoscopic prostatectomy

Prostate cancer remains a significant health problem worldwide and is the second highest cause of cancer-related death in men. While there is uncertainty over which men will benefit from radical treatment, considerable efforts are being made to reduce treatment related side-effects and in optimising outcomes. This article reviews the development and introduction of robotic-assisted laparoscopic radical prostatectomy (RALP), the results to date, and the possible future directions of RALP